Therapeutic agent for motor disorders

Abstract

Provided are an agent for the treatment and/or prophylaxis of a movement disorder, the agent for the treatment and/or prophylaxis wherein the movement disorder is extrapyramidal syndrome, the agent for the treatment and/or prophylaxis wherein the movement disorder is bradykinesia, gait disturbance, dystonia, dyskinesia or tardive dyskinesia, the agent for the treatment and/or prophylaxis wherein the movement disorder is a side effect of L-DOPA and/or dopamine agonist therapy, and the like, each containing a thiazole derivative represented by the formula (I) wherein R 1 represents aryl and the like, and R 2 represents pyridyl or the like, or a pharmaceutically acceptable salt thereof as an active ingredient.

1 - 11 . (canceled) 
     
     
         12 . A pharmaceutical composition comprising:
 (a) a thiazole derivative represented by formula (I)   
       
         
           
           
               
               
           
         
       
       wherein R 1  represents aryl, aralkyl, an aromatic heterocyclic group, aromatic heterocycle-alkyl, aliphatic heterocycle-alkyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen; lower alkyl optionally substituted by lower alkoxy or morpholino; lower alkoxy; lower alkanoyl; and vinyl, and R 2  represents pyridyl or tetrahydropyranyl, or a pharmaceutically acceptable salt thereof, and
 (b) L-DOPA and/or a dopamine agonist. 
 
     
     
         13 . The pharmaceutical composition according to  claim 12 , wherein R 1  is phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy and ethoxy, or a pharmaceutically acceptable salt thereof. 
     
     
         14 . The pharmaceutical composition according to  claim 13 , wherein R 2  is pyridyl, or a pharmaceutically acceptable salt thereof. 
     
     
         15 . The pharmaceutical composition according to  claim 13 , wherein R 2  is tetrahydropyranyl, or a pharmaceutically acceptable salt thereof. 
     
     
         16 . The pharmaceutical composition according to  claim 12 , wherein the thiazole derivative is represented by formulas (IA)-(IAA): 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         17 - 22 . (canceled) 
     
     
         23 . A kit, comprising:
 (a) a first component comprising a thiazole derivative represented by formula (I)   
       
         
           
           
               
               
           
         
       
       wherein R 1  represents aryl, aralkyl, an aromatic heterocyclic group, aromatic heterocycle-alkyl, aliphatic heterocycle-alkyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen; lower alkyl optionally substituted by lower alkoxy or morpholino; lower alkoxy; lower alkanoyl; and vinyl, and R 2  represents pyridyl or tetrahydropyranyl, or a pharmaceutically acceptable salt thereof, and
 (b) a second component comprising L-DOPA and/or a dopamine agonist. 
 
     
     
         24 . The kit according to  claim 23 , wherein R 1  is phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy and ethoxy, or a pharmaceutically acceptable salt thereof. 
     
     
         25 . The kit according to  claim 24 , wherein R 2  is pyridyl, or a pharmaceutically acceptable salt thereof. 
     
     
         26 . The kit according to  claim 24 , wherein R 2  is tetrahydropyranyl, or a pharmaceutically acceptable salt thereof. 
     
     
         27 . The kit according to  claim 23 , wherein the thiazole derivative is represented by one of formulas (IA)-(IAA): 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         28 . A method of treating and/or preventing progression of a movement disorder, comprising the steps of:
 administering to a patient an effective amount of a thiazole derivative represented by formula (I)   
       
         
           
           
               
               
           
         
       
       wherein R 1  represents aryl, aralkyl, an aromatic heterocyclic group, aromatic heterocycle-alkyl, aliphatic heterocycle-alkyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen; lower alkyl optionally substituted by lower alkoxy or morpholino; lower alkoxy; lower alkanoyl; and vinyl, and R 2  represents pyridyl or tetrahydropyranyl,
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         29 . The method according to  claim 28 , wherein R 1  is phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy and ethoxy, or a pharmaceutically acceptable salt thereof. 
     
     
         30 . The method according to  claim 29 , wherein R 2  is pyridyl, or a pharmaceutically acceptable salt thereof. 
     
     
         31 . The method according to  claim 29 , wherein R 2  is tetrahydropyranyl, or a pharmaceutically acceptable salt thereof. 
     
     
         32 . The method according to  claim 28 , wherein the thiazole derivative is represented by any one of formulas (IA)-(IAA): 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         33 . The method according to  claim 28 , wherein the movement disorder is extrapyramidal syndrome. 
     
     
         34 . The method according to  claim 28 , wherein the movement disorder is bradykinesia, gait disturbance, dystonia, dyskinesia or tardive dyskinesia. 
     
     
         35 . The method according to  claim 28 , wherein the movement disorder is a side effect of L-DOPA and/or dopamine agonist therapy. 
     
     
         36 . The method according to  claim 35 , wherein the side effect is a motor complication. 
     
     
         37 . The method according to  claim 36 , wherein the motor complication is wearing-off phenomenon. 
     
     
         38 . The method according to  claim 36 , wherein the motor complication is on-off fluctuation. 
     
     
         39 . A method of treating and/or preventing progression of Parkinson's disease, comprising the steps of:
 administering to a patient simultaneously or separately at an interval (a) an effective amount of a thiazole derivative represented by formula (I)   
       
         
           
           
               
               
           
         
       
       wherein R 1  represents aryl, aralkyl, an aromatic heterocyclic group, aromatic heterocycle-alkyl, aliphatic heterocycle-alkyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen; lower alkyl optionally substituted by lower alkoxy or morpholino; lower alkoxy; lower alkanoyl; and vinyl, and R 2  represents pyridyl or tetrahydropyranyl, or a pharmaceutically acceptable salt thereof, and
 (b) an effective amount of L-DOPA and/or a dopamine agonist. 
 
     
     
         40 . The method according to  claim 39 , wherein R 1  is phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy and ethoxy, or a pharmaceutically acceptable salt thereof. 
     
     
         41 . The method according to  claim 40 , wherein R 2  is pyridyl, or a pharmaceutically acceptable salt thereof. 
     
     
         42 . The method according to  claim 40 , wherein R 2  is tetrahydropyranyl, or a pharmaceutically acceptable salt thereof. 
     
     
         43 . The method according to  claim 39 , wherein the thiazole derivative is represented by any one of formulas (IA)-(IAA): 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         44 - 54 . (canceled) 
     
     
         55 . A compound represented by any one of the following formulas (IE)-(IAA), or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         56 . A combination of:
 (a) a thiazole derivative represented by formula (I)   
       
         
           
           
               
               
           
         
       
       wherein R 1  represents aryl, aralkyl, an aromatic heterocyclic group, aromatic heterocycle-alkyl, aliphatic heterocycle-alkyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen; lower alkyl optionally substituted by lower alkoxy or morpholino; lower alkoxy; lower alkanoyl; and vinyl, and R 2  represents pyridyl or tetrahydropyranyl, or a pharmaceutically acceptable salt thereof, and
 (b) L-DOPA and/or a dopamine agonist, for use in the treatment and/or prophylaxis of Parkinson's disease. 
 
     
     
         57 . The combination according to  claim 56 , wherein (a) and (b) are administered simultaneously. 
     
     
         58 . The combination according to  claim 56 , wherein R 1  is phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl or tetrahydropyranyloxy, each of which is optionally substituted by 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy and ethoxy, or a pharmaceutically acceptable salt thereof. 
     
     
         59 . The combination according to  claim 58 , wherein R 2  is pyridyl, or a pharmaceutically acceptable salt thereof. 
     
     
         60 . The combination according to  claim 58 , wherein R 2  is tetrahydropyranyl, or a pharmaceutically acceptable salt thereof. 
     
     
         61 . The combination according to  claim 56 , wherein the thiazole derivative is represented by any one of formulas (IA)-(IAA): 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         62 - 73 . (canceled) 
     
     
         74 . The combination according to  claim 56 , wherein (a) and (b) are administered separately at an interval. 
     
     
         75 - 78 . (canceled)